In order to investigate the role of long noncoding RNA (lncRNA) DLX6-AS1 in macrophage pyrop-tosis and its related mechanism, the downstream microRNAs (miRNAs) of DLX6-AS1 and the target genes of miRNAs were analyzed in THP-1 cell line by bioinformatics analysis, real-time fluorescent quantitative PCR (qRT-PCR), a dual-luciferase reporter system, and so on. The effects of DLX6-AS1 and downstream miR-15 on macrophage pyroptosis were detected by immunofluorescence staining. The results showed that the expression of DLX6-AS1 was up-regulated in pyroptotic macrophages, and knocking down DLX6-AS1 inhibited pyroptosis of macrophages, which, however, could be reversed by miR-15 inhibitor. Further studies found that miR-15 inhibited macrophage pyroptosis by regulating the target gene caspase-1. These results indicated that DLX6-AS1 induces macrophage pyroptosis by competitively binding to miR-15 and removing the inhibition of miR-15 on its target gene caspase-1. The experiments will enrich the theoretical basis of lncRNA in regulating macrophage pyroptosis.